In this project the detailed morphology of neurons, neuroglia and the neuropil of prefrontal cortex will be examined to ascertain what changes take place during normal aging of rhesus monkey cortex, and to determine which of these changes can be correlated with cognitive changes displayed by particular monkeys. This will involve a determination of whether there is an overall loss of cortical neurons with age, and specifically, whether numbers of GABAergic neurons and their axon terminals change. The latter will be assessed initially, by examining the population of inhibitory axon terminals synapsing with the cell bodies of pyramidal cells. Layer I will also be examined for changes in dendritic trees of pyramidal cells and the deep cortical layers for degeneration of myelinated axons. Senile plaques will be examined to determine the events that signal their formation, what neuronal and neuroglial elements contribute to them as the plaques mature, and how the mix of these elements changes. Antibodies to neurotransmitters and structural proteins, as well as Golgi impregnation will be utilized to label specific elements contributing to plaques, since almost nothing is known about their fine structure, origins, whether elements within them are regenerating, or degenerating, and how they mature to a stable state. This kind of information is necessary to understand the aging process in the cerebral cortex, before useful attempts can be made to retard the process.